环氧合酶-2、P-gp在胃癌组织中的表达及其意义

目的　探讨环氧合酶 2 (COX 2 )在胃癌组织中的表达及其对P糖蛋白 (P gp)表达的影响。 方法　应用免疫组织化学方法 ,检测 48例胃癌及 10例正常胃组织中COX 2与P gp的表达。 结果　正常胃组织中未见COX 2表达 ,胃癌组织中COX 2表达阳性率为 60 .4% ( 2 9/ 48) ,其阳性表达与肿瘤的TNM分期及淋巴结转移相关 (P <0 .0 5 )。COX 2阳性组中P gp表达阳性率为 82 .8% ( 2 4/ 2 9) ,而COX 2阴性组P gp同时阴性表达率为 63 .2 % ( 12 / 19) ,两者表达呈高度正相关 (γ =0 .470 ,P <0 .0 1)。 结论COX 2表达参与胃癌的发生及恶性进展 ,并可能通过干预P gp的表达参与对肿瘤多药耐药 (MDR)的调节作用     

胃癌及胃溃疡组织中环氧合酶2的表达

目的　探讨环氧合酶 2 (cyclooxygenase 2 ,COX 2 )蛋白在胃癌组织、正常胃黏膜组织以及胃溃疡组织中的表达及其意义。方法　应用免疫组化方法 (SP法 )检测 3 6例胃癌组织及其癌旁正常胃黏膜组织以及 12例胃溃疡组织中COX 2蛋白的表达。结果　胃癌组织中COX 2蛋白的表达水平显著高于癌旁正常胃黏膜及胃溃疡组织 ,差异具有显著性 (P <0 0 1) ;有淋巴结转移的胃癌组织中COX 2蛋白的表达水平高于无淋巴结转移者 ,差异具有显著性 (P <0 0 5 ) ;Ⅲ Ⅳ期胃癌组织的COX 2蛋白的阳性表达水平明显高于Ⅰ Ⅱ期 ,差异具有显著意义 (P <0 0 5 )。结论　COX 2蛋白的过表达参与了胃癌的演进。     

环氧合酶-2及其抑制剂与肺癌耐药的研究进展

环氧合酶-2（COX-2）是环氧合酶的可诱导形式,在非小细胞肺癌尤其是腺癌中过度表达,并参与肺癌耐药性的产生,降低肿瘤细胞对化疗药物的敏感性。COX-2抑制剂有抗肿瘤并预防肿瘤形成的作用,因此,为逆转肺癌的耐药性,提高肺癌患者的生存率并改善其预后,将COX-2抑制剂作为辅助化疗药物并与化疗药物联合的应用成为了肺癌治疗的新方向。     

乳腺癌组织中COX-2与MDR1/P-gp表达的相关性研究

目的:探讨环氧化酶-2(COX-2)蛋白与P糖蛋白(P-gp)在乳腺癌组织中表达的相关性。方法:应用免疫组织化学染色法,检测32例乳腺癌组织中COX-2蛋白与P-gp蛋白的表达情况。结果:32例乳腺癌组织中COX-2表达阳性率为62·5%(20/32),P-gp表达阳性率为46·9%(15/32),两者表达呈正相关性(r=0·598,P<0·05)。结论:乳腺癌组织中COX-2与P-gp表达呈正相关,COX-2可干预P-gp的表达并参与乳腺癌多药耐药(MDR)的调节。     

环氧合酶-2在胃癌与癌前病变和其他胃黏膜组织中表达的研究

目的:研究胃癌与癌前病变和其他胃黏膜组织中环氧合酶-2(COX-2)的表达情况,探讨COX-2蛋白作为肿瘤分子标记物对胃癌和癌前病变进行辅助诊断的意义.方法:收集胃镜活检的正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、胃黏膜肠化生、胃黏膜不典型性增生和胃癌组织,用免疫组织化学染色法检测COX-2蛋白在各种组织中的阳性表达情况.以正常胃黏膜组织和正常兔血清作阴性对照.结果:COX-2蛋白在胃癌前病变和和胃癌组织中的表达阳性率为48%-84%.胃癌和胃黏膜不典型性增生标本中COX-2蛋白表达阳性率显著高于正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎和胃黏膜肠上皮化生标本(P<0.05).而胃癌组织COX-2蛋白表达的阳性率与胃黏膜不典型性增生组之间无显著性差异(P>0.05).此外,慢性萎缩性胃炎和胃黏膜肠化生标本与正常胃黏膜和慢性浅表性胃炎标本之间COX-2蛋白表达阳性率亦有显著性差异(P<0.05);所有病变组的COX-2蛋白表达阳性率均比正常胃黏膜组显著性地升高 (P<0.05).结论:胃癌与癌前病变组织中COX-2蛋白的表达显著升高,COX-2蛋白可作为肿瘤标记物对胃癌和胃癌前病变进行辅助诊断.     

胃癌组织中c-erbB-2与P-gp表达的相关性研究

目的了解胃癌组织中c-erbB-2表达与多药耐药的相关性及其临床意义。方法采用免疫组化方法检测了98例胃癌组织中c-erbB-2表达,应用流式细胞术(FCM)检测癌细胞P-糖蛋白(P-gp)水平,并对其进行相关性分析。结果胃癌组织中c-erbB-2阳性表达33例,阳性率33.67%;P-gp阳性表达58例,阳性率59.18%。在c-erbB-2表达阴性的病例累及2～3个部位的癌比累及1个部位癌的P-gp表达增多,两组比较有显著性差异(P=0.035)。当c-erbB-2和P-gp表达双阳性时,P-gp表达增多与双阴性组比较有非常显著性差异(P<0.001);当c-erbB-2或P-gp表达单阳性时,P-g表达增多与双阴性组比较有非常显著性差异(P<0.001);胃癌c-erbB-2和P-gp表达与患者年龄、性别、临床分期、胃癌分化程度和3年生存情况分析,均无统计学意义。结论同时检测胃癌c-erbB-2和P-gp表达水平,可为胃癌的综合治疗及化疗药物选择提供临床参考依据。但是不能用来判断胃癌患者预后。     

环氧合酶-2与肿瘤多药耐药

肿瘤细胞的多药耐药性（MDR）是肿瘤患者化疗失败的主要原因。MDR是指肿瘤细胞同时对多种化学结构和作用机制并不相同的抗癌药物产生的耐受性,MDR涉及众多分子参与。近来研究表明,环氧合酶-2（cyclooxygenase-2,COX-2）可能在肿瘤细胞的MDR中发挥重要作用,非甾体类消炎药可能通过逆转MDR、增强肿瘤细胞对化疗药物的敏感性而发挥联合抑瘤作用。全文重点对COX-2在肿瘤多药耐药中作用的研究进展进行综述。     

环氧合酶-2 与白血病

 环氧合酶-2（COX-2）是体内前列腺素（PG）合成过程中的主要限速酶,在人类白血病细胞中有不同程度的表达,并且可能与白血病的发生、发展有关。选择性COX-2 抑制剂有望成为白血病的化疗及靶向治疗新药物。现就COX-2在白血病发病机制中的作用及选择性COX-2抑制剂在白血病中的应用进行综述。     

选择性环氧合酶-2 抑制剂 NS-398 抑制多药耐药细胞株 P-糖蛋白表达

目的:探讨选择性环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂NS-398对多药耐药细胞株K562/ADM细胞P-糖蛋白(P-glycoprotein,P-gp)表达的影响。方法:K562/ADM细胞经浓度分别为10μmol/L、20μmol/L、40μmol/L、80μmol/L、160μmol/L的NS-398处理,24h、48h、72h后用RT-PCR法检测MDR1mRNA的表达、用流式细胞仪检测mdr1蛋白表达。结果:随着NS-398浓度的升高以及作用时间延长,MDR1mRNA、p-gp表达降低,不同浓度的药物与测量时间之间存在着交互作用(P<0.05)。结论:选择性环氧合酶-2抑制剂NS-398可抑制K562/ADM细胞的MDR1/P-gp表达。     

Study on the relationship between P-glycoprotein （P-gp） and C-erbB-2 expression in gastric carcinoma

Objective： To understand the relationship between C-erbB-2 and multidrug resistance （MDR） as well as its clinical significance. Methods： P-gp level was detected by flow cytometry and simultaneously to examine the C-erbB-2 expression level by immunohistochemistry assay in the operating samples. Their relationship was analyzed from 59 cases with gastric carcinoma. Results： The P-gp positive expression was 38/59 （64.4%） cases with gastric carcinoma. The C-erbB-2 positive expression was 21/59 （35.6%） cases with gastric carcinoma. From the analysis of the P-gp and C-erbB-2 relationship, which was involving, range in the gastric carcinoma, that involving two or three sites were more than the site one, in the cases with C-erbB-2 negative. Compared this two groups, there was a significant difference （P = 0.026）. When the C-erbB-2 was positive, the P-gp expression had a significant difference （P = 0.04） in comparing the Ⅲ-Ⅳ stage （lymph node metastasis） with Ⅰ-Ⅱ stage （without lymph node metastasis）. The tumor＇s size, differentiation degree, ages and sex were not related to the C-erbB- 2 and P-gp expression. Conclusion： High level of P-gp expression was related to the C-erbB-2 positive expression in clinical Ⅲ-Ⅳ stage patient with gastric carcinoma （lymph node metastasis）. It suggested that the double positive patient might be a poor prognosis. However, when the C-erbB-2 was negative expression, the clinical staging （with lymph node metastasis） was not related to the P-gp expression in gastric carcinoma patients.     

胃癌细胞P-gp与C-erbB-2表达相关性研究

Objective:To understand the relationship between C-erbB-2 and multidrug resistance(MDR)as well as its clinical significance.Methods:P-gp level was detected by flow cytometry and simultaneously to examine the C-erbB-2 expression level by immunohistochemistry assay in the operating samples.Their relationship was analyzed from 59 cases with gastric carcinoma. Results:The P-gp positive expression was 38/59(64.4%)cases with gastric carcinoma.The C-erbB-2 positive expression was 21/59(35.6%)cases with gastric carcinoma From the analysis of the P-gp and C-erbB-2 relationship,which was involving,range in the gastric carcinoma,that involving two or three sites were more than the site one,in the cases with C-erbB-2 negative.Compared this two groups,there was a significant difierence(P=0.026).When the C-erbB-2 was positive,the P-gp expression had a significant difierence(P=0.04)in comparing the Ⅲ-Ⅳ stage(lymph node metastasis)with Ⅰ-Ⅱ stage(without lymph node metastasis).The lumor's size,differentiation degree,ages and sex were not related to the C-erbB-2 and P-gp expression.Conclusion:High level of p-gp expression was related to the C-erbB-2 positive expression in clinical Ⅲ-Ⅳ stage patient with gastric carcinoma (lymph node metastasis).It suggested that the double positive patient might be a poor prognosis.However,when the C-erbB-2 was negative expression,the clinical staging(with lymph node metastasis)was not related to the p-gp expression in gastric carcinoma patients.     

环氧化酶-2在肝细胞肝癌中的表达及与多药耐药的相关性研究

目的观察环氧化酶-2（COX-2）、P糖蛋白（P-gp）在肝细胞肝癌（HCC）中的表达并分析两者的相关性。方法应用免疫组化S-P法、逆转录多聚酶链反应法（RT-PCR）检测重庆医科大学附属第二医院2005年10月～2007年6月手术切除经病理证实的52例HCC标本、癌旁组织及10例正常肝组织中COX-2和P-gp及其基因的表达情况。结果COX-2/COX-2 mRNA、P-gp/MDR1 mRNA在肝细胞肝癌组织中的表达明显上调,与其在正常肝组织、癌旁组织中的表达比较差异有统计学意义（P〈0.01）。且COX-2、P-gp在肝细胞肝癌中的阳性表达具有明显相关性,相关系数r=0.563（P〈0.01）。结论（1）COX-2高表达参与了肝癌的发生、发展。（2）COX-2与P-gp在肝细胞肝癌中的表达密切相关,COX-2可能干预P-gp的表达从而参与肝癌的多药耐药过程。     

Study on the Relationship between P-glycoprotein and CD44 Expression in Gastric Carcinoma

Objective： Investigation of the relationship between P-glycoprotein （P-gp） and adhesion molecule CD44 as well as their clinical significance in gastric carcinoma. Methods： To examine the expressed level of P-gp and CD44 in 98 cases with gastric carcinoma by flow eytometry and evaluate their relationships with elinieopathologieal factors. Results： Among the 98 gastric carcinomas, 40 cases （40.8%） were P-gp negative （positive cells 〈25%）; 14 cases （14.2%） were 25%-40% expression of P-gp positive cells; 17 cases （17.3%） were 41%-60% expression of P-gp positive cells; 27 cases （27.5%） were the high expression （positive cells 〉60%） of P-gp in all patients with gastric carcinoma. When the tumor sizes were more than 6 cm, the P-gp positive of CD44 showed a significant difference （P〈0.05） in 35 cases with P-gp positive, compared with it in 24 cases with P-gp negative. When the tumors were in low-moderate differentiated gastric carcinoma, the expression of CD44 showed a significant difference （P〈0.05） in 44 cases with P-gp positive, as compared with it in 30 cases with P-gp negative. When the patients were in clinical Ⅲ-Ⅳ stage, the expression of CD44 showed a significant difference （P〈0.05） in 42 cases with P-gp positive, as compared with it in 30 cases with P-gp negative. When the patients with lymph node metastasis, their CD44 expression showed a significant difference （P〈0.05） in 46 cases with P-gp positive, compared with it in 32 cases with P-gp negative. When the tumors P-gp expressed positive, their CD44 expression will be increase. Conclusion： When the CD44 and P-gp both have the positive high expression, it will be significantly associated with the gastric carcinoma progression and metastasis, so both were a positive expression in gastric carcinoma, it might suggest a poor and unfavorable prognosis result.     

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis

OBJECTIVE: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis. METHODS: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was calculated by counting of CD34-positive vascular endothelial cells. RESULTS: The positive expression rates of COX-2, MMP-9 and MVD in the cancerous tissue were 80.2%, 74.0%, and 32.5 +/- 8.3, respectively, which were significantly higher than those in the normal tissue (P < 0.01). COX-2, MMP-9 expression rates and MVD in the patients with stages III and IV were 91.4%, 84.5% and 34.9 +/- 8.7, respectively, which were significantly higher than those in the patients with stages I and II (P < 0.01). In addition, the Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 (r = 0.311, P < 0.01) and MMP-9 (r = 0.349, P < 0.01) expressions. CONCLUSIONS: Overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in the gastric carcinoma. These results provide evidence that COX-2 contribute to gastric cancer development by promoting MMP-9 expression and angiogenesis.     

胃癌P-糖蛋白表达及其临床意义

采用免疫组织化学ABC法检测78例胃癌组织中多药材药基因产物P-糖蛋白。探讨胃癌组织中P-糖蛋白表达水平及其临床意义。结果表明,P-糖蛋白在胃癌组织中表达阳性率为42．3％（33／78）。P-糖蛋白表达在胄癌各临床分期、大体形态及组织学类型之间无显著性差异。胃癌组织中P-糖蛋白表达提示胃癌与多药耐药表型有关化疗药物的先天性耐药有关,可能是胃癌临床化疗疗效较低的重要原因。     

胃癌细胞凋亡与p53蛋白异常相关性研究

采用ＤＮＡ末端转移酶介导的Ｂｉｏ－ｄＵＴＰ原位末端标记技术（ＴＵＮＥＬ）和免疫组织化学技术，分别对６０例胃癌标本的细胞凋亡和ｐ５３蛋白异常作同步研究和相关性分析。结果在６０例胃癌组织中细胞凋亡指数为１．８％～１９．４％（平均９．３±３．９％），ｐ５３蛋白异常表达率为６３．３％（３８／６０）；ｐ５３蛋白阳性组细胞凋亡指数为３．７±１．１％（１．８％～７．９％），而ｐ５３蛋白阴性组细胞凋亡指数１４．７±２．４％（７．４％～１９．４％），两组间有显著性差异。结果表明胃癌中存在较高频率的ｐ５３蛋白异常和细胞凋亡，ｐ５３蛋白异常与胃癌细胞凋亡间存在着负相关性     

COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究

背景与目的:P糖蛋白(P-glycoprotein,P-gp)高表达是复发淋巴瘤患者化疗失败的主要原因之一,有研究表明,P-gp呈环氧合酶-2(cyclooxygenase-2,COX-2)依赖性表达上调.本研究旨在通过检测COX-2与P-gp在B细胞非霍奇金淋巴瘤(B-cell non-Hodgkin's lymphoma,B-NHL)中的表达及其相关性,并初步观察两者表达与淋巴瘤临床特征之间的关系.方法:采用逆转录-聚合酶链反应及免疫组化SP法检测COX-2及P-gp在43例初治B-NHL、27例复发B-NHL中的表达.结果:COX-2和P-gp在初治B-NHL中的阳性率分别为23.3%(10/43)和11.6%(5/43),而在复发B-NHL中的阳性率分别为74.1%(20/27)和70.4%(19/27),差异有统计学意义(P＜0.01),且两者表达在复发B-NHL中呈显著正相关(r=0.998,P＜0.01).侵袭性B-NHL中的COX-2和P-gp表达均高于惰性B-NHL(P＜0.05).结论:COX-2和P-gp在复发B-NHL中高表达,可能与肿瘤转移有关.     

胃癌组织和胃周淋巴结COX-2 mRNA的表达及其意义

目的:探讨胃癌组织和胃周淋巴结内环氧化酶-2(COX-2)mRNA的表达特点及其意义。方法:选取胃癌患者43例和正常胃粘膜组织15例,取癌灶、癌旁、淋巴结和正常胃粘膜标本,通过采用PCR(Real-timeSemi-quantitativePCR)方法检测COX-2mRNA表达。结果:1)癌灶处COX-2mRNA表达高于癌旁和正常胃粘膜组织的表达;2)癌旁COX-2mRNA表达高于正常胃粘膜组织的表达(P<0.05);3)侵透浆膜的胃癌组织COX-2mRNA表达高于未透浆膜的表达;4)弥漫生长的胃癌组织COX-2mRNA表达高于团块状及巢状生长者的表达(P<0.05);5)淋巴结转移阳性的淋巴结组织COX-2表达高于淋巴结转移阴性的表达(P<0.05)。结论:胃癌组织COX-2mRNA的表达明显升高,其表达与胃癌生物学行为相关;胃癌周围淋巴结组织COX-2mRNA的表达情况可作为推测癌周淋巴结有无微小转移癌的一个具有提示意义的参考指标。